C-reactive protein across pregnancy in individuals exposed to childhood maltreatment: The role of psychological and physical sequelae of maltreatment.

BACKGROUND: Childhood maltreatment (CM) has long-term consequences for the regulation of stress biology which are particularly pronounced when mental and physical health sequelae have manifested. C-reactive protein (CRP) has been shown to be elevated in the non-pregnant state in association with CM as well as in the setting of CM-associated mental and physical health sequelae. In pregnancy, however, the association between CM and CRP is less clear. We sought to examine this association and consider the moderating role of four common health sequelae of CM (maternal depressive symptoms, overweight/obesity, smoking, and hypertensive disorders during pregnancy). METHODS: A prospective, longitudinal study of 744 healthy pregnant participants was conducted, with analyses focusing on a sample of 643 participants. CM was assessed with the Childhood Trauma Questionnaire (CTQ) and categorized by whether no vs. one or more moderate to severe CM experiences were reported. Blood serum concentrations of CRP, maternal depression severity (continuous scores of the Center for Epidemiologic Studies Depression Scale, CES-D) and smoking during pregnancy were assessed in early (16.52 ± 2.50 weeks gestation) and late (33.65 ± 1.18 weeks gestation) pregnancy. Pre-pregnancy body mass index (BMI) was obtained at the first study visit and hypertensive disorders diagnosed during pregnancy were obtained from the medical record. Linear mixed effects models were employed to assess main effects of CM as well as interactive effects of CM and four common CM-associated sequelae as well as a sum score of these sequelae on repeatedly measured CRP concentration. In secondary analyses, we conducted latent class analyses to classify participants based on their specific experiences of childhood abuse and/or neglect and to assess the association of these CM subgroups with CM sequelae and CRP. All analyses were adjusted for potential confounders (maternal race and ethnicity and education/income). RESULTS: CRP concentration decreased from early to late pregnancy (B = -0.06, SE = 0.01, p < 0.001). While there was no main effect of CM on CRP (p = 0.49), the interaction of CM and depressive symptoms was associated with CRP concentration (B = 0.08, SE = 0.04, p < 0.05), indicating higher CRP across pregnancy with increasing levels of depressive symptoms during pregnancy in participants with CM experience. This interaction was mainly driven by participants with co-occurring physical and emotional maltreatment. For none of the other CM-associated sequelae a statistically significant interaction with CM on CRP concentration was observed. CONCLUSIONS: These results add to the growing empirical evidence suggesting higher inflammation during pregnancy in participants exposed to CM who experience depressive symptoms and highlight the detrimental effects of multiple co-occurring experiences of maltreatment. Given the negative consequences of chronic inflammatory state for the mother and the developing fetus, monitoring and treating psychiatric sequelae during pregnancy among participants exposed to CM is potentially an important opportunity to dampen long-term detrimental effects of CM, serving at least two generations.

Adaptation of Screening Tools for Social Determinants of Health in Pregnancy: A Pilot Project.

OBJECTIVES: Social determinants of health (SDOH) and stress during pregnancy may contribute to adverse pregnancy outcomes. The objective of this in the field pilot project was to develop a comprehensive screening tool by combining existing validated screeners. Additionally, implement use of this tool within routine prenatal visits and assess feasibility. METHODS: Pregnant patients accessing prenatal care at a single site of an urban Federally Qualified Health Center were recruited during prenatal visits to complete a Social Determinants of Health in Pregnancy Tool (SIPT). SIPT combines a series of questions from existing and well-validated tools and consists of five domains: (1) perceived stress, (2) relationship and family stress, (3) domestic violence, (4) substance abuse, and (5) financial stress. RESULTS: Between April 2018 and March 2019, 135 pregnant participants completed SIPT. Ninety-one percent of patients scored positive on at least one screener, 54% to three or more screeners. CONCLUSIONS: Despite guidelines to screen for SDOH during pregnancy there is no universal tool. Our pilot project demonstrated the concurrent use of adapted screening tools where participants reported at least one area of potential stress, and that linking to resources at the time of a visit is plausible. Future work should examine if screening and point of care linkages of services improves maternal child outcomes.

The intersection of race and socioeconomic status is associated with inflammation patterns during pregnancy and adverse pregnancy outcomes.

BACKGROUND: Preterm birth rates are higher among individuals of lower socioeconomic status and non-White race, which is possibly related to life-course stressors. It is important to understand the underlying mechanisms of these health disparities, and inflammation is a possible pathway to explain the disparities in birth outcomes. OBJECTIVE: In this study, we aimed to determine whether patterns of inflammation differed by maternal race and socioeconomic status. STUDY DESIGN: Seven hundred and forty-four participants in a multi-site, prospective study of pregnancy and birth outcomes provided biological and psychological data between 12'0-20'6 weeks gestation. Participants with recent infection, fever, antibiotics or steroid treatment were excluded. Cytokines including INFÉ£, IL-10, IL-13, IL-6, IL-8, and TNFα, and the acute phase protein CRP were measured in serum and values and were log-transformed for normality when appropriate, and a non-orthogonal rotation (Oblimid) was performed to allow the extracted factor to inter-correlate. IFNγ, IL-8, IL-10, IL-6, TNF-a, and IL-13 loaded onto Inflammatory Factor 1 (IF-1), while CRP and IL-6 loaded onto Inflammatory Factor 2 (IF-2). Race and education were collected via self-report during an in-person study visit. Multivariable models were used to determine the association of race and SES with IF-1 and IF-2 during the second trimester, and a mediation model was used to examine if inflammation is on the causal pathway. Models were adjusted for study site, prenatal age, pre-pregnancy BMI, smoking during pregnancy, and gestational age at the time of blood collection. RESULTS: Six hundred and five participants were included in our final analysis, with 61.2% of low or moderate SES, and 35.5% identifying as a person of color (POC). Identifying as a POC, being of low and moderate SES, and being both low-SES and POC or moderate-SES and POC were associated with higher odds of preterm birth and lower birth weight percentile infants. Low SES POC participants had significantly higher IF-1 and IF-2 scores when compared to high-SES White participants. Additionally, higher IF-1 and IF-2 were associated with shorter gestation. In the mediation analysis, we observed a significant direct effect of race/SES on preterm birth; however, the results did not support an indirect pathway where IF-1 or IF-2 acted as mediators. CONCLUSION: Maternal race and SES are significantly associated with inflammatory biomarkers during pregnancy, and when race and SES are considered in combination, they are stronger predictors of adverse pregnancy outcomes than when evaluated separately.

Using principal component analysis to examine associations of early pregnancy inflammatory biomarker profiles and adverse birth outcomes.

OBJECTIVE: Inflammation as a risk factor for preterm birth is well-established. The primary objective of this analysis was to examine whether individual cytokines versus a composite indicator of mid-pregnancy inflammation are significantly associated with risk for adverse birth outcomes. STUDY DESIGN: A multi-site prospective study was conducted in a socio-demographically diverse cohort of 610 pregnant participants. At a study visit between 12 and 20 6/7 weeks' gestation, low-grade inflammation was measured via log-transformed serum concentrations of the biomarkers IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α, and CRP. Principal component analysis (PCA) was used to identify underlying dimensions of inflammatory activity from the seven biomarkers measured. Gestational age and birth weight at delivery were obtained from medical chart review. The associations between inflammatory profiles and birth outcomes were assessed via linear and logistic regression models. Results were compared with those from individual inflammatory biomarkers, and model fit was assessed using Akaike's Information Criterion (AIC). RESULTS: Principal component analysis analysis yielded a two-factor solution, with the first factor (IF1) composed of IL-8, IL-10, IL-13, IFN-É£, and TNF-α, and the second factor (IF2) containing IL-6 and CRP. When adjusted for race, education, BMI, smoking status, gestational age at time of blood draw, and study site, a one standard deviation (SD) increase in IF1 remained significantly associated with a decrease in standardized gestational age (ß = -.13, 95% CI: -.21, -.05) and an increase in odds of preterm delivery (OR = 1.46, 95% CI: 1.13, 1.88) (Table 3). A one SD increase in IF2 was similarly associated with a decrease in standardized gestational age at delivery (ß = -.13, 95% CI: -.23, -.04) and an increase in odds of preterm delivery (OR: 1.46, 95% CI: 1.04, 2.05). Neither IF1 nor IF2 was associated with measures of fetal growth. AIC identified that IL-6 was a slightly better fit for length of gestation compared to either composite measure, though all performed similarly. CONCLUSION: Independent of known sociodemographic risk factors, an elevated mid-pregnancy inflammatory profile was associated with a nearly 50% increase in odds of preterm delivery. The composite performed similarly to IL-6. These results suggest that maternal low-grade inflammation is a risk factor for preterm delivery, and that mid-pregnancy inflammatory biomarkers may be useful in predicting risk for preterm delivery.

Lifetime Psychosocial Stress Exposure Associated with Hypertensive Disorders of Pregnancy.

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) complicate 5 to 10% of all pregnancies and are a major cause of pregnancy-related morbidity. Exposure to psychosocial stress has been associated with systemic inflammation and adverse birth outcomes in pregnant women. Thus, it is probable that psychosocial stress and inflammation play a role in the development of HDP. The primary objective of this analysis was to determine if a woman's lifetime psychosocial stress exposure was associated with an increased risk of HDP. Additionally, we examined whether serum inflammation was an underlying biological mediator for this relationship. STUDY DESIGN: A multisite prospective study was conducted in a sociodemographically diverse cohort of 647 pregnant women. At a study visit between 12 and 206/7 weeks' gestation, maternal psychosocial stress was assessed with six validated assessments and inflammation was measured via log-transformed serum concentrations of interferon-γ, interleukin (IL)-10, IL-13, IL-6, IL-8, and tumor necrosis factor-α. A composite stress score was calculated for each participant from the six stress assessments. The diagnosis of HDP was abstracted from the medical record and was defined as the presence of gestational hypertension after 20 weeks of pregnancy and/or preeclampsia. The association between composite stress and HDP was determined using binary logistic regression. Inflammation, using the six inflammatory biomarkers, was tested as a potential mediator between stress and HDP. RESULTS: Participants with higher composite stress scores were more likely to develop HDP (odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.06-2.12). When adjusted for known risk modifiers, including maternal age, race/ethnicity, parity, pre-pregnancy body mass index, diabetes, chronic hypertension, and smoking during pregnancy, the risk remained unchanged (OR: 1.50, 95% CI: 1.03-2.20). No mediation effect by inflammation was observed. CONCLUSION: Independent of known risk factors, women exposed to greater composite stress burden across the life course are at increased risk of developing HDP. KEY POINTS: · This study was conducted to determine if women with high levels of psychosocial stress have differences in risk for hypertensive disorders of pregnancy (HDP).. · Independent of known risk factors, women with increased lifetime psychosocial burden are at higher risk for HDP.. · A model that captures multiple domains of life stress may better predict HDP than a unimodal stress assessment..

Early Term Delivery and Breastfeeding Outcomes.

OBJECTIVE: Higher rates of adverse outcomes have been reported for early term (37 0 to 38 6 weeks) versus full term (≥ 39 0 weeks) infants, but differences in breastfeeding outcomes have not been systematically evaluated. This study examined breastfeeding initiation and exclusivity in early and full term infants in a large US based sample. METHODS: This secondary analysis included 743 geographically- and racially-diverse women from the Measurement of Maternal Stress Study cohort, and 295 women from a quality assessment at a hospital-based clinic in Evanston, IL. Only subjects delivering ≥ 37 weeks were included. Initiation of breastfeeding (IBF) and exclusive breastfeeding (EBF) were assessed via electronic medical record review after discharge. Associations of IBF and EBF with early and full term delivery were assessed via univariate and multivariate logistic regression. RESULTS: Among 872 women eligible for inclusion, 85.7% IBF and 44.0% EBF. Early term delivery was not associated with any difference in frequency of IBF (p = 0.43), but was associated with significantly lower odds of EBF (unadjusted OR 0.61, 95% CI 0.466, 0.803, p < 0.001). This association remained significant (adjusted OR 0.694, 95% CI 0.515, 0.935, p = 0.016) after adjusting for maternal diabetes, hypertensive disorders of pregnancy, cesarean delivery, maternal age, race/ethnicity, parity, Medicaid status, NICU admission, current smoking, and delivery hospital. CONCLUSIONS FOR PRACTICE: Despite comparable breastfeeding initiation frequencies, early term infants were significantly less likely to be exclusively breastfed compared to full term infants. These data suggest that women with early term infants may benefit from counseling regarding the potential for breastfeeding difficulties as well as additional breastfeeding support after delivery.